| 1. |
- Nowak-Sliwinska, Patrycja, et al.
(författare)
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Consensus guidelines for the use and interpretation of angiogenesis assays
- 2018
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Ingår i: Angiogenesis. - : Springer. - 0969-6970 .- 1573-7209. ; 21:3, s. 425-532
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Forskningsöversikt (refereegranskat)abstract
- The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
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| 2. |
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| 4. |
- Courtois, A, et al.
(författare)
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Positron Emission Tomography/Computed Tomography Predicts and Detects Complications After Endovascular Repair of Abdominal Aortic Aneurysms
- 2019
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Ingår i: Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists. - : SAGE Publications. - 1545-1550. ; 26:4, s. 520-528
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To assess if aortic 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) could play a role in predicting complications after endovascular aneurysm repair (EVAR). Materials and Methods: This study involved 2 cohorts of men with abdominal aortic aneurysm treated by EVAR: those who underwent a PET/CT scan before EVAR (n=17) and those who had a PET/CT during follow-up (n=34). Uptake of FDG was measured as the standardized uptake value (SUV). D-dimer, a marker of fibrinolysis, was measured in blood drawn concomitantly with the PET/CT. Results: A significant uptake of FDG in the aneurysm wall was detected by PET/CT before EVAR in 6 of 17 patients. During the first year after EVAR, type II endoleaks developed in 5 of these FDG+ patients vs 3 of 11 FDG– patients (p=0.04). Two of the FDG+ patients had continued sac growth and required conversion to open repair. A significant association between sac growth rate, SUV, and the presence of endoleak was found in the 34 patients who underwent PET/CT after EVAR. Finally, D-dimer was significantly increased in patients with both endoleak and positive PET/CT in the post-EVAR group. Conclusion: This study suggests that the presence of FDG uptake in the aortic wall might be a useful tool to predict patients at high risk of developing post-EVAR complications.
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| 8. |
- Maegdefessel, L, et al.
(författare)
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miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development
- 2014
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 5214-
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Tidskriftsartikel (refereegranskat)abstract
- Identification and treatment of abdominal aortic aneurysm (AAA) remain among the most prominent challenges in vascular medicine. MicroRNAs (miRNAs) are crucial regulators of cardiovascular pathology and represent intriguing targets to limit AAA expansion. Here we show, by using two established murine models of AAA disease along with human aortic tissue and plasma analysis, that miR-24 is a key regulator of vascular inflammation and AAA pathology. In vivo and in vitro studies reveal chitinase 3-like 1 (Chi3l1) to be a major target and effector under the control of miR-24, regulating cytokine synthesis in macrophages as well as their survival, promoting aortic smooth muscle cell migration and cytokine production, and stimulating adhesion molecule expression in vascular endothelial cells. We further show that modulation of miR-24 alters AAA progression in animal models, and that miR-24 and CHI3L1 represent novel plasma biomarkers of AAA disease progression in humans.
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| 9. |
- Sorelius, Karl, et al.
(författare)
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The Microbiology of Infective Native Aortic Aneurysms in a Population-Based Setting
- 2022
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Ingår i: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 78, s. 112-122
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to describe the microbiology of surgically treated infective native (mycotic) aortic aneurysms (INAAs), and associated survival and development of infection-related complications (IRCs). Methods: Data were pooled from 2 nationwide studies on surgically treated patients with INAAs in Sweden, between 1994 - 2016. Patients were grouped and analyzed according to culture results: 1) Staphylococcus aureus, 2) Streptococcus species (sp.), 3) Salmonella sp., 4) Enterococcus sp., 5) Gram-negative intestinal bacteria, 6) Other sp. (all other species found in culture), and 7) Negative cultures. Results: A sum of 182 patients were included, mean age 71 years (standard deviation; SD: 8.9). The median follow-up was 50.3 months (range 0 - 360). 128 (70.3%) patients had positive blood and/or tissue culture; Staphylococcus aureus n = 38 (20.9%), Streptococcus sp. n = 37 (20.3%), Salmonella sp. n = 19 (10.4%), Enterococcus sp. n = 16 (8.8%), Gram-negative intestinal bacteria n = 6, (3.3%), Other sp. n = 12 (6.6%) and Negative cultures n = 54 (29.7%). The estimated survival for the largest groups at 2-years after surgery was: Staphylococcus aureus 62% (95% Confidence interval 53.9 - 70.1), Streptococcus sp. 74.7% (67.4 - 82.0), Salmonella sp. 73.7% (63.6 - 83.8), Enterococcus sp. 61.9% (49.6 - 74.2), and Negative cultures 89.8% (85.5 - 94.1), P =.051. There were 37 IRCs (20.3%), and 19 (51.4%) were fatal, the frequency was insignificant between the groups. The majority of IRCs, 30/37 (81%), developed during the first postoperative year. Conclusion: In this assessment of microbiological findings of INAAs in Sweden, 50% of the pathogens were Staphylococcus aureus, Streptococcus sp., or Salmonella sp.. The overall 20%-frequency of IRCs, and its association with high mortality, motivates long-term antibiotic treatment regardless of microbial findings.
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| 10. |
- Steuer, Johnny, et al.
(författare)
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Editor's Choice - Durability of Endovascular Repair in Blunt Traumatic Thoracic Aortic Injury : Long-Term Outcome from Four Tertiary Referral Centers
- 2015
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 50:4, s. 460-465
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To analyze the early and long-term survival and re-intervention rate in patients undergoing TEVAR for blunt traumatic thoracic aortic injury. Methods: This was a consecutive case series. Between the years 2001 and 2010, a total of 74 patients underwent TEVAR for blunt traumatic thoracic aortic injury at four tertiary referral centers, three in Sweden and one in Switzerland. The median age of the patients was 41 years, and 16% were women. Demographic, procedural, and outcome data were collected and reviewed retrospectively. The patients were followed up during 2013-2014. Results: Early (30 day) mortality was 9% (7 patients), with only two cases directly related to the aortic injury; in hospital mortality was 14% as three patients died during the primary hospital admission within the first 6 months. Most patients had sustained severe injuries to other organ systems, and among all in hospital deaths brain injury was the predominant cause. Five year survival in the whole group was 81%. Re-intervention was needed in 16% (12 patients) during the first year, half of them within the first month. Only one patient underwent re-intervention more than 1 year after the initial procedure. Infolding and partial stentgraft collapse was the reason for the secondary procedure in five of the 13 patients; in three it occurred within 3 weeks of the acute TEVAR. Conclusion: TEVAR allows rapid and effective therapy in trauma patients with blunt aortic injury. The outcome is dependent on the severity of the concomitant injuries. The treatment is durable during the first decade after the procedure, but even longer follow up is needed to determine the impact of TEVAR in young patients on the degenerative changes that take place in the aging aorta.
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| 11. |
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| 12. |
- Öhman, Lena, 1967, et al.
(författare)
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Acellular Bordetella pertussis vaccine enhances mucosal interleukin-10 production, induces apoptosis of activated Th1 cells and attenuates colitis in Galphai2-deficient mice.
- 2005
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 141:1, s. 37-46
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Tidskriftsartikel (refereegranskat)abstract
- Mice deficient for the inhibitory G protein subunit alpha2 (Galphai2(-/-)) spontaneously develop a progressive inflammatory bowel disease resembling ulcerative colitis, and have a T helper 1 (Th1)-dominated immune response prior to onset of colitis, which is further augmented after the onset of disease. The present study was performed to investigate whether the Galphai2(-/-) mice were able to down-regulate the Th1-dominated inflammatory mucosal immune response and/or induce an anti-inflammatory Th2/T regulatory response and thereby diminish the severity of colitis following treatment with acellular Bordetella pertussis vaccine. The acellular vaccine against B. pertussis, the causative agent of whooping cough, has been demonstrated to induce a Th2-mediated response in both man and mice. We therefore treated Galphai2(-/-) mice intraperitoneally with a three-component acellular B. pertussis vaccine. The treated Galphai2(-/-) mice showed significantly increased interleukin (IL)-10 production in intestinal tissue, associated with significantly reduced colitis and decreased mortality, compared to untreated Galphai2(-/-) mice. The attenuation of colitis in Galphai2(-/-) mice was due, at least partly, to the B. pertussis surface antigen filamentous haemagglutinin (FHA), which almost completely inhibited proliferation of CD4(+) T cells and stimulated apoptosis of activated CD4(+) T helper 1 cells. In conclusion, the three-component acellular B. pertussis vaccine containing filamentous haemagglutinin increases the production of IL-10 in the intestinal mucosa, induces apoptosis of activated Th1 cells and attenuates colitis in Galphai2(-/-) mice.
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| 13. |
- Andersson, Mattias, et al.
(författare)
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A population-based study of post-endovascular aortic repair rupture during 15 years
- 2021
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Ingår i: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 74:3
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The devastating event of a ruptured abdominal aortic aneurysm (rAAA) in patients who have survived a previous AAA repair, either elective or urgent, is a feared and quite uncommon event. It has been suggested to partly explain the loss of the early survival benefit for endovascular aortic repair (EVAR) vs open surgical repair (OSR). The main objective of this study was to report the national incidence rate, risk factors and outcome of post-EVAR ruptures. Secondarily, the national incidence rate of ruptures after OSR (post-OSR ruptures) was investigated. Methods: We conducted a nationwide, population-based, retrospective cohort study using the inpatient and outpatient entries for all patients >40 years of age, receiving their first (index) surgical procedure for AAA, from 2001 to 2015. Only patients surviving their index procedure were included. The primary outcome was rAAA, registered after discharge from the index procedure (EVAR or OSR), identified in the Swedish National Patient Registry and the Cause of Death Registry. Results: In total, 14,859 patients survived their primary (index) AAA procedure. There were 6470 EVAR procedures, 5893 for intact AAA (iAAA) and 577 for rAAA. Of the 6470 EVAR patients, 86 cases of post-EVAR rupture were identified, corresponding with a cumulative incidence of 1.3% over a mean follow-up time of 3.9 years. The incidence rate was 3.4 (95% confidence interval [CI], 2.7-4.2)/1000 person-years. The independent risk factors identified for post-EVAR rupture were rAAA at index surgery HR 2.4 (95% CI, 1.4-4.1, p 0.002) and age (hazard ratio, 1.1; 95% CI, 1.0-1.1; P <.001). Freedom from post-EVAR rupture was 99%, 98%, and 96% at 3, 5, and 10 years, respectively. Total and postoperative mortality after post-EVAR rupture were 42% and 17% (30 days), 45% and 22% (90 days), and 53% and 33% (1 year). The incidence rate of post-OSR rupture was 0.9/1000 person-years (95% CI, 0.7-1.2). Conclusions: Post-EVAR rupture is a rare complication that can occur at any time after the index EVAR procedure. This finding may have implications for the discussion of limited follow-up programs and for the choice of procedure in patients with an AAA with a long life expectancy. An rAAA as the indication for the index surgery and age were identified as risk factors for post-EVAR rupture. The mortality associated with post-EVAR rupture is high, but lower than that of primary rAAA. The much lower risk of post-OSR rupture was confirmed, but must not be neglected as a possible late complication. © 2021 The Authors
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| 21. |
- Cegelski, Lynette, et al.
(författare)
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Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation
- 2009
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Ingår i: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 5:12, s. 913-919
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Tidskriftsartikel (refereegranskat)abstract
- Curli are functional extracellular amyloid fibers produced by uropathogenic Escherichia coli (UPEC) and other Enterobacteriaceae. Ring-fused 2-pyridones, such as FN075 and BibC6, inhibited curli biogenesis in UPEC and prevented the in vitro polymerization of the major curli subunit protein CsgA. The curlicides FN075 and BibC6 share a common chemical lineage with other ring-fused 2-pyridones termed pilicides. Pilicides inhibit the assembly of type1pili, which are required for pathogenesis during urinary tract infection. Notably, the curlicides retained pilicide activities and inhibited both curli-dependent and type 1–dependent biofilms. Furthermore, pretreatment of UPEC with FN075 significantly attenuated virulence in a mouse model of urinary tract infection. Curli and type 1pili exhibited exclusive and independent roles in promoting UPEC biofilms, and curli provided a fitness advantage in vivo. Thus, the ability of FN075 to block the biogenesis of both curli and type 1pili endows unique anti-biofilm and anti-virulence activities on these compounds.
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| 22. |
- Cervin, Anne, 1971-, et al.
(författare)
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Results After Open and Endovascular Repair of Popliteal Aneurysm: A Matched Comparison Within a Population Based Cohort
- 2021
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 61:6, s. 988-997
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify factors affecting the outcome after open surgical (OSR) and endovascular (ER) repair of popliteal artery aneurysm (PA) in comparable cohorts. Methods: A matched comparison in a national, population based cohort of 592 legs treated for PA (2008 - 2012), with long term follow up. Registry data from 899 PA patients treated in 2014 - 2018 were analysed for time trends. The 77 legs treated by ER were matched, by indication, with 154 legs treated with OSR. Medical records and imaging were collected. Analysed risk factors were anatomy, comorbidities, and medication. Elongation and angulations were examined in a core lab. The main outcome was occlusion. Results: Patients in the ER group were older (73 vs. 68 years, p = .001), had more lung disease (p = .012), and were treated with dual antiplatelet therapy or anticoagulants more often (p < .001). The hazard ratio (HR with 95% confidence intervals) for occlusion was 2.69 (1.60 - 4.55, p < .001) for ER, but 3.03 (1.26 - 7.27, p = .013) for poor outflow. For permanent occlusion, the HR after ER was 2.47 (1.35 - 4.50, p = .003), but 4.68 (1.89 - 11.62, p < .001) for poor outflow. In the ER subgroup, occlusion was more common after acute ischaemia (HR 2.94 [1.45 - 5.97], p = .003; and poor outflow HR 14.39 [3.46 - 59.92], p < .001). Larger stent graft diameter reduced the risk (HR 0.71 [0.54 - 0.93], p = .014). In Cox regression analysis adjusted for indication and stent graft diameter, elongation increased the risk (HR 1.020 per degree [1.002 - 1.033], p = .030). PAS treated for acute ischaemia had a median stent graft diameter of 6.5 mm, with those for elective procedures being 8 mm (p < .001). Indications and outcomes were similar during both time periods (2008 - 2012 and 2014 - 2018). Conclusion: In comparable groups, ER had a 2.7 fold increased risk of any occlusion, and 2.4 fold increased risk of permanent occlusion, despite more aggressive medical therapy. Risk factors associated with occlusion in ER were poor outflow, smaller stent graft diameter, acute ischaemia, and angulation/elongation. An association between indication, acute ischaemia, and small stent graft diameter was identified.
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| 23. |
- Cervin, Anne, et al.
(författare)
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Treatment of Popliteal Aneurysm by Open and Endovascular Surgery: A Contemporary Study of 592 Procedures in Sweden
- 2015
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1532-2165 .- 1078-5884. ; 50:3, s. 342-350
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Tidskriftsartikel (refereegranskat)abstract
- WHAT THIS STUDY ADDS Previous comparisons between open and endovascular repair of popliteal aneurysms have focused on asymptomatic patients, and have short follow up. This study is strengthened by the fact that it is contemporary, population based, without any selection bias, reporting on all kinds of presentations, and has approximately 90% 1 year follow up data. It shows that endovascular repair has significantly inferior results compared with open repair, in particular in the group of patients who present with acute ischaemia. We believe these results will make many vascular surgeons think twice before they treat patients endovascularly in the future. Background: Popliteal aneurysm (PA) is traditionally treated by open repair (OR). Endovascular repair (ER) has become more common. The aim was to describe time trends and compare results (OR/ER). Methods: The Swedish vascular registry, Swedvasc, has a specific PA module. Data were collected (2008-2012) and supplemented with a specific protocol (response rate 99.1%). Data were compared with previously published data (1994-2002) from the same database. Results: The number of operations for PA was 15.7/million person-years (8.3 during 1994-2001). Of 592 interventions for PA (499 patients), 174 (29.4%) were treated for acute ischaemia, 13 (2.2%) for rupture, 105 (17.7%) for other symptoms, and 300 (50.7%) were asymptomatic (31.5% were treated for acute ischaemia, 1994-2002, p = .58). There were no differences in background characteristics between OR and ER in the acute ischaennia group. The symptomatic and asymptomatic groups treated with ER were older (p = .006, p < .001). ER increased 3.6 fold (4.7% 1994-2002, 16.7% 2008-2012, p = .0001). Of those treated for acute ischaemia, a stent graft was used in 27 (16.4%). Secondary patency after ER was 70.4% at 30 days and 47.6% at 1 year, versus 93.1% and 86.8% after OR (p = .001, < .001). The amputation rate at 30 days was 14.8% after ER, 3.7% after OR (p = .022), and 17.4% and 6.8% at 1 year (p = .098). A stent graft was used in 18.3% for asymptomatic PA. Secondary patency after ER was 94.5% at 30 days and 83.7% at 1 year, compared with 98.8% and 93.5% after OR (p = .043 and 0.026). OR was performed with vein graft in 87.6% (395/451), with better primary and secondary patency at 1 year than prosthetic grafts (p = .002 and < .001), and with a posterior approach in 20.8% (121/581). Conclusions: The number of operations for PA doubled while the indications remained similar. ER patency was inferior to OR, especially after treatment for acute ischaemia, and the amputation risk tended to be higher, despite similar pre-operative characteristics. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of European Society for Vascular Surgery. This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/4.0/).
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| 24. |
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| 25. |
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| 27. |
- D'Oria, M, et al.
(författare)
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The "Vascular Surgery COVID-19 Collaborative" (VASCC)
- 2020
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Ingår i: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. - : Elsevier BV. - 1532-2165. ; 60:3, s. 489-490
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 28. |
- Eifert, S, et al.
(författare)
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Applying the Gender Lens to Risk Factors and Outcome after Adult Cardiac Surgery
- 2014
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Ingår i: Viszeralmedizin. - : S. Karger AG. - 1662-6664. ; 30:2, s. 99-106
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background: </i></b>Applying the gender lens to risk factors and outcome after adult cardiac surgery is of major clinical interest, as the inclusion of sex and gender in research design and analysis may guarantee more comprehensive cardiovascular science and may consecutively result in a more effective surgical treatment as well as cost savings in cardiac surgery. <b><i>Methods: </i></b>We have reviewed classical cardiovascular risk factors (diabetes, arterial hypertension, hyperlipidemia, smoking) according to a gender-based approach. Furthermore, we have examined comorbidities such as depression, renal insufficiency, and hormonal influences in regard to gender. Gender-sensitive economic aspects have been evaluated, surgical outcome has been analyzed, and cardiovascular research has been considered from a gender perspective. <b><i>Results: </i></b>The influence of typical risk factors and outcome after cardiac surgery has been evaluated from a gender perspective, and the gender-specific distribution of these risk factors is reported on. The named comorbidities are listed. Economic aspects demonstrated a gender gap. Outcome after coronary and valvular surgeries as well as after heart transplantation are displayed in this regard. Results after postoperative use of intra-aortic balloon pump are shown. Gender-related aspects of clinical and biomedical cardiosurgical research are reported. <b><i>Conclusions: </i></b>Female gender has become an independent risk factor of survival after the majority of cardiosurgical procedures. Severely impaired left ventricular ejection fraction independently predicts survival in men, whereas age does in females.
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| 29. |
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| 31. |
- Falk, A, et al.
(författare)
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Depression as a predictor of postoperative delirium after cardiac surgery: a systematic review and meta-analysis
- 2021
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Ingår i: Interactive cardiovascular and thoracic surgery. - : Oxford University Press (OUP). - 1569-9285. ; 32:3, s. 371-379
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVESDepression is common in patients with cardiac disease. The importance of preoperative depression for development of postoperative delirium (POD) following cardiac surgery is not well known. The aim is to provide a summary estimate of depression as a predictor of POD following cardiac surgery.METHODSSystematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science Core Collection and Psycinfo (Ovid) was performed from inception to October 2019, including cohort studies reporting odds ratios (ORs) and 95% confidence intervals (CIs) for POD following cardiac surgery in patients with preoperative depression compared to patients without depression. ORs and 95% CIs for POD were calculated using random-effects meta-analyses. Subgroup and sensitivity analyses were performed.RESULTSSeven studies were included with a combined study population of 2066 patients. The pooled prevalence of POD in the combined study population was 26% and preoperative depression was present in ∼9% of the total study population. All studies showed a positive association between preoperative depression and POD; and in 5 studies, the association was statistically significant. Patients with depression had a pooled OR of 2.31 (95% CI 1.37–3.90) for POD.CONCLUSIONSThis systematic review and meta-analysis confirm the findings that the previous association between preoperative depression and increased risk for developing POD reported for other patient groups is found also in cardiac surgery. Depression screening prior to cardiac surgery may be effective in identifying patients at higher risk for POD.
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| 36. |
- Flentie, Kelly, et al.
(författare)
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Chemical disarming of isoniazid resistance in Mycobacterium tuberculosis
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : The National Academy of Scionces of the United States of America. - 0027-8424 .- 1091-6490. ; 116:21, s. 10510-10517
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Tidskriftsartikel (refereegranskat)abstract
- Mycobacterium tuberculosis (Mtb) killed more people in 2017 than any other single infectious agent. This dangerous pathogen is able to withstand stresses imposed by the immune system and tolerate exposure to antibiotics, resulting in persistent infection. The global tuberculosis (TB) epidemic has been exacerbated by the emergence of mutant strains of Mtb that are resistant to frontline antibiotics. Thus, both phenotypic drug tolerance and genetic drug resistance are major obstacles to successful TB therapy. Using a chemical approach to identify compounds that block stress and drug tolerance, as opposed to traditional screens for compounds that kill Mtb, we identified a small molecule, C10, that blocks tolerance to oxidative stress, acid stress, and the frontline antibiotic isoniazid (INH). In addition, we found that C10 prevents the selection for INH-resistant mutants and restores INH sensitivity in otherwise INH-resistant Mtb strains harboring mutations in the katG gene, which encodes the enzyme that converts the prodrug INH to its active form. Through mechanistic studies, we discovered that C10 inhibits Mtb respiration, revealing a link between respiration homeostasis and INH sensitivity. Therefore, by using C10 to dissect Mtb persistence, we discovered that INH resistance is not absolute and can be reversed.
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| 37. |
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| 38. |
- Gjertsson, Inger, 1962, et al.
(författare)
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Are B lymphocytes of importance in severe Staphylococcus aureus infections?
- 2000
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Ingår i: Infection and immunity. - 0019-9567. ; 68:5, s. 2431-4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the role of B cells in experimental, superantigen-mediated Staphylococcus aureus arthritis and sepsis, we used gene-targeted B-cell-deficient mice. The mice were inoculated intravenously with a toxic shock syndrome toxin 1 (TSST-1)-producing S. aureus strain. The B-cell-deficient and thus agamma-globulinemic mice showed striking similarities to the wild-type control animals with respect to the development of arthritis, the mortality rate, and the rate of bacterial clearance. Surprisingly, we found that the levels of gamma interferon in serum were significantly lower (P < 0. 0001) in B-cell-deficient mice than in the controls, possibly due to impaired superantigen presentation and a diminished expression of costimulatory molecules. In contrast, the levels of interleukin-4 (IL-4), IL-6, and IL-10 in serum were equal in both groups. Our findings demonstrate that neither mature B cells nor their products significantly contribute to the course of S. aureus-induced septic arthritis.
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| 39. |
- Grdic Eliasson, Dubravka, et al.
(författare)
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The mucosal adjuvant effects of cholera toxin and immune-stimulating complexes differ in their requirement for IL-12, indicating different pathways of action.
- 1999
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Ingår i: European journal of immunology. - 0014-2980. ; 29:6, s. 1774-84
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Tidskriftsartikel (refereegranskat)abstract
- Adjuvants that can improve mucosal vaccine efficacy are much warranted. In this comparative study between cholera toxin (CT) and immune-stimulating complexes (ISCOM) we found that, contrary to CT, ovalbumin (OVA)-ISCOM were poor inducers of mucosal anti-OVA IgA responses, but induced similar or better systemic immunity following oral immunizations. The addition of CT to the oral OVA-ISCOM protocol did not stimulate local anti-OVA IgA immunity, nor did it change the quality or magnitude of the systemic responses. Both vectors recruited strong innate immunity, but only OVA-ISCOM could directly induce IL-12, demonstrable at the protein and mRNA levels. CT had no inhibitory effects on lipopolysaccharide/IFN-gamma-induced IL-12 mRNA expression or IL-12 production. Furthermore, adjuvanticity of CT was unaffected in IL-12-deficient mice, while OVA-ISCOM showed partly impaired adjuvant effects by the lack of IL-12. CT abrogated the induction of oral tolerance stimulated by antigen feeding in these mice. In addition, CT did not alter TGF-beta levels, suggesting that the immunomodulating effect of CT was independent of IL-12 as well as TGF-beta production. Taken together, these findings indicate that mucosal adjuvanticity of CT and ISCOM are differently dependent on IL-12, suggesting that separate and distinct antigen-processing pathways are involved.
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| 40. |
- Götlind, Yu-Yuan Chiu, 1964, et al.
(författare)
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Interplay between Th1 and Th17 effector T cell pathways in the pathogenesis of spontaneous colitis and colon cancer in the Gai2-deficient mouse
- 2013
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Ingår i: International Immunology. - Oxford, United Kingdom : Oxford University Press. - 0953-8178 .- 1460-2377. ; 25:1, s. 35-44
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Tidskriftsartikel (refereegranskat)abstract
- Gαi2-deficient mice spontaneously develop colitis. Using xMAP technology and RT-PCR, we investigated cytokine/chemokine profiles during histologically defined phases of disease: (i) no/mild, (ii) moderate, (iii) severe colitis without dysplasia/cancer and (iv) severe colitis with dysplasia/cancer, compared with age-matched wild-type (WT) littermates. Colonic dysplasia was observed in 4/11 mice and cancer in 1/11 mice with severe colitis. The histology correlated with progressive increases in colon weight/cm and spleen weight, and decreased thymus weight, all more advanced in mice with dysplasia/cancer. IL-1β, IL-6, IL-12p40, IL-17, TNF-α, CCL2 and CXCL1 protein levels in colons, but not small intestines increased with colitis progression and were significantly increased in mice with moderate and severe colitis compared with WT mice, irrespective of the absence/presence of dysplasia/cancer. CCL5 did not change during colitis progression. Colonic IL-17 transcription increased 40- to 70-fold in all stages of colitis, whereas IFN-γ mRNA was gradually up-regulated 12- to 55-fold with colitis progression, and further to 62-fold in mice with dysplasia/cancer. IL-27 mRNA increased 4- to 15-fold during the course of colitis, and colonic IL-21 transcription increased 3-fold in mice with severe colitis, both irrespective of the absence/presence of dysplasia/cancer. FoxP3 transcription was significantly enhanced (3.5-fold) in mice with moderate and severe colitis, but not in mice with dysplasia/cancer, compared with WT mice. Constrained correspondence analysis demonstrated an association between increased protein levels of TNF-α, CCL2, IL-1β, IL-6 and CXCL1 and dysplasia/cancer. In conclusion, colonic responses are dominated by a mixed T(h)1/T(h)17 phenotype, with increasing T(h)1 cytokine transcription with progression of colitis in Gαi2(-/-) mice.
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| 41. |
- Halasz, R, et al.
(författare)
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Relation between GB virus C/hepatitis G virus and fulminant hepatic failure may be secondary to treatment with contaminated blood and/or blood products
- 1999
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 44:2, s. 274-278
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Tidskriftsartikel (refereegranskat)abstract
- The role of the recently discovered GB virus C (GBV-C)/hepatitis G virus in fulminant hepatic failure (FHF) has been debated. Although GBV-C RNA has been detected in many cases of FHF, recent data suggest that the relation between GBV-C and FHF may be accidental.AimsTo retrospectively investigate the possible relation between the presence of GBV-C markers (RNA or antibodies to the GBV-C envelope 2 (E2) glycoprotein) and FHF.MethodsThe presence of GBV-C RNA was determined in serum samples from 58 patients diagnosed with FHF using a reverse transcriptase polymerase chain reaction. Amplified genetic fragments were directly sequenced by the dideoxy chain termination method. Antibodies to GBV-C in serum samples were detected by enzyme immunoassay based on a recombinant GBV-C E2 protein.ResultsNine (16%) patients with FHF had GBV-C RNA and 14 (24%) had GBV-C E2 antibodies, which are higher frequencies than in healthy subjects (p<0.01 and p<0.05 respectively). Seven of ten patients with GBV-C markers during FHF tested negative for these markers before therapy with blood and/or blood products. Sequence analysis of the GBV-C NS3 region fragments of six FHF patients showed no common sequence pattern or motif.ConclusionsThe frequencies of both GBV-C RNA and antibodies are higher in patients with FHF than in healthy subjects. However, these increased frequencies may in many cases be explained by the use of contaminated blood and/or blood products given as therapy.
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| 42. |
- Hannan, T. J., et al.
(författare)
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Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis
- 2014
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 1:1, s. 46-57
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Tidskriftsartikel (refereegranskat)abstract
- The spread of multidrug-resistant microorganisms globally has created an urgent need for novel therapeuticstrategies to combat urinary tract infections (UTIs). Immunomodulatory therapy may provide benefit, as treatmentof mice with dexamethasone during acute UTI improved outcome by reducing the development of chroniccystitis, which predisposes to recurrent infection. Herewe discovered soluble biomarkers engaged inmyeloid celldevelopment and chemotaxis that were predictive of future UTI recurrence when elevated in the sera of youngwomen with UTI. Translation of these findings revealed that temperance of the neutrophil response early duringUTI, and specifically disruption of bladder epithelial transmigration of neutrophils by inhibition ofcyclooxygenase-2, protected mice against chronic and recurrent cystitis. Further, proteomics identified bladderepithelial remodeling consequent to chronic infection that enhances sensitivity to neutrophil damage. Thus, cyclooxygenase-2 expression during acute UTI is a critical molecular trigger determining disease outcome anddrugs targeting cyclooxygenase-2 could prevent recurrent UTI.
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| 43. |
- Hedin, U, et al.
(författare)
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Jesper Swedenborg In Memoriam
- 2017
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Ingår i: EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY. - : Elsevier BV. - 1078-5884. ; 53:5, s. 615-616
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 44. |
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| 45. |
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| 46. |
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| 48. |
- Hultgren, R., et al.
(författare)
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Cost-effectiveness of targeted screening for abdominal aortic aneurysm in siblings
- 2019
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 106:3, s. 206-216
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population screening for abdominal aortic aneurysm (AAA) in 65‐year‐old men has been shown to be cost‐effective. A risk group with higher prevalence is siblings of patients with an AAA. This health economic model‐based study evaluated the potential cost‐effectiveness of targeted AAA screening of siblings.Methods: A Markov model validated against other screening programmes was used. Two methods of identifying siblings were analysed: direct questioning of patients with an AAA (method A), and employing a national multigeneration register (method B). The prevalence was based on observed ultrasound data on AAAs in siblings. Additional parameters were extracted from RCTs, vascular registers, literature and ongoing screening. The outcome was cost‐effectiveness, probability of cost‐effectiveness at different willingness‐to‐pay (WTP) thresholds, reduction in AAA death, quality‐adjusted life‐years (QALYs) gained and total costs on a national scale.Results_ Methods A and B were estimated to reduce mortality from AAA, at incremental cost‐effectiveness ratios of €7800 (95 per cent c.i. 4627 to 12 982) and €7666 (5000 to 13 373) per QALY respectively. The probability of cost‐effectiveness was 99 per cent at a WTP of €23 000. The absolute risk reduction in AAA deaths was five per 1000 invited. QALYs gained were 27 per 1000 invited. In a population of ten million, methods A and B were estimated to prevent 12 and 17 AAA deaths, among 2418 and 3572 siblings identified annually, at total costs of €499 500 and €728 700 respectively.Conclusion: The analysis indicates that aneurysm‐related mortality could be decreased cost‐effectively by applying a targeted screening method for siblings of patients with an AAA.
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